Caenorhabditis elegans-тағы DAF-2 гені және ұзақ өмір сүру жолдары

Protein coding gene in the species Caenorhabditis elegans

The DAF 2 gene encodes for the insulin like growth factor 1 (IGF 1) receptor in the worm Caenorhabditis elegans. DAF 2 is part of the first metabolic pathway discovered to regulate the rate of aging. DAF 2 is also known to regulate reproductive development, resistance to oxidative stress, thermotolerance, resistance to hypoxia, and resistance to bacterial pathogens. Mutations in DAF 2 and also Age 1 have been shown by Cynthia Kenyon to double the lifespan of the worms. In a 2007 episode of WNYC’s Radiolab, Kenyon called DAF 2 "the grim reaper gene.”

Long lived DAF 2 C. elegans mutants are resistant to the oxidizing agent paraquat and to UV light. DAF 2 mutants also have a higher DNA repair capability than wild type C. elegans. DAF 2 is the only member of the insulin receptor family in C. elegans but it corresponds, in form and function, to multiple pathways in humans. The protein predicted from DAF 2's sequence is 35% identical to the human insulin receptor, which regulates metabolism; 34% identical to the IGF 1 receptor, which regulates growth; and 33% identical to the human insulin receptor–related receptor. In C. elegans, the insulin/IGF 1/FOXO pathway is initiated by changes in IGF 1 levels which cause IGF 1 receptors to start a phosphorylation cascade that deactivates the FOXO transcription factor, DAF 16. When not phosphorylated, DAF 16 is active and present in the nucleus. DAF 16 is responsible for up regulating transcription of about 100 genes that code for cell protecting products such as heat shock proteins and antioxidants. Genetic analysis reveals that the presence of functioning DAF 16 is required to produce the extended lifespan observed in DAF 2 knock downs.

Caenorhabditis elegans, which progresses through a series of larval stages into a final reproductive adult, may instead enter a less metabolically active dauer diapause stage if food scarcity or overcrowding occurs before reaching adulthood.